Thin layer chromatographic compatibility study in preformulation of new transdermal therapeutic systems

Transdermal drug delivery systems of indapamide have been formulated by using solvent casting method. Monolithic systems were prepared by using hydroxy propyl methyl cellulose (HPMC) and ethyl cellulose (EC) polymers by incorporating glycerine and dibutyl phthalate as plasticizers, respectively. All the patches were uniform with respect to physicochemical and scanning electron microscopy (SEM) evaluation. Th e in vitro drug release studies indicated that HPMC containing fi lms have shown better release than that of EC containing fi lms without any permeation enhancer. A total of eight monolithic systems were prepared by using a drug polymer ratio of 1:4 and incorporated diff erent vegetable oils as permeation enhancers in diff erent concentrations. Th e prepared systems released the drug in the following order: F3 > F4 > F7 > F5 > F8 > F6 > F1 > F2. Th e various permeation parameters such as fl ux, permeability coeffi cient, enhancement ratio and diff usion rate constants were determined for all the formulations. Th e maximum fl ux of 9.08 × 102 mg/ cm2 h was observed with HPMC monolithic system containing 30% w/w olive oil. A signifi cant improvement of fl ux was observed in the following order: olive oil > linseed oil > sunfl ower oil > cottonseed oil > coconut oil > castor oil. Further improvement of fl ux was observed, when 30% w/w olive oil was applied directly onto the skin prior to the studies. Th e in vitro release studies revealed that the release was sustained up to 24 h and it follows zero-order kinetics. All the fi lms were found to be stable at 37°C and 45°C with respect to their physical parameters and drug content. Key words: EC, HPMC, linseed oil, olive oil, permeation enhancers, sunfl ower oil, transdermal

The objective of this study was to develop sustained release (SR) matrix tablets of metoprolol succinate (MS), by using different polymer combinations and fillers, to optimize by response surface methodology and to evaluate biopharmaceutical parameters of the optimized product. Matrix tablets of various combinations were prepared with cellulose-based polymers: hydroxy propyl methyl cellulose (HPMC) and ethyl cellulose (EC); and lactose and dibasic calcium phosphate dihydrate (DCP) as fillers. Study of pre-compression and post-compression parameters facilitated the screening of a formulation with best characteristics that underwent here optimization study by response surface methodology (Central Composite Design). The optimized tablet was subjected to further study like scanning electron microscopy, swelling study and in vivo study in rabbit model. Both in vitro and in vivo study revealed that combining of HPMC K100M (21.95%) with EC (8.85%), and use of DCP as filler sustained the action up to 12 h. The in vivo study of new SR tablets showed significant improvement in the oral bioavailability of MS in rabbits after a single oral dose of 25 mg. The delayed Tmax and lower Cmax indicated a slow and SR of MS from the optimized matrix tablets in comparison with the immediate release dosage form. The developed SR (MS) tablet of improved efficacy can perform therapeutically better than conventional tablet.

Background: In the present investigation, tamoxifen-loaded liposomes transdermal patch was formulated using eudragit-RL, hydroxypropyl methyl cellulose K-50, and ethyl cellulose. Materials and Methods: Liposomes were formulated by solvent evaporation method using poly (sebacic acid-co-ricinoleic acid) in varying ratios and evaluated for particle size, drug loading, entrapment efficiency, transmission electron microscopy, differential scanning calorimetry, and X-ray diffraction. Formulated tamoxifen-loaded liposomes were finally incorporated into transdermal patch and evaluated for thickness drug content, moisture content, moisture uptake, folding endurance, tensile strength diffusion coefficient, permeability coefficient, in vitro permeation, and skin irritation. Optimized transdermal patches were tested for its pharmacokinetic and pharmacodynamics parameters Results: Formulated transdermal patches showed improved bioavailability of tamoxifen when compared to its oral route. Conclusion: Tamoxifen-loaded liposomal transdermal patches could serve as a better alternative to existing marketed formulation in terms of bioavailability.

Aim and Background:Domperidone is a dopamine antagonist with antiemetic properties having a plasma half life of 7-9 h with 15% oral bioavailability. In the present work transdermal patches of domperidone were prepared with the objective to improve its therapeutic efficacy, patient compliance and to reduce the frequency of dosing and side effects, as well as to avoid its extensive first pass metabolism of the drug.Materials and Methods:The patches were prepared using ethyl cellulose (EC): Poly vinyl pyrrolidone (PVP), poly vinyl alcohol (PVA): Poly vinyl pyrrolidone (PVP) and hydroxypropylmethylcellulose (HPMC): Sodium (carboxy methyl cellulose) CMC as polymers in combination. The physicochemical parameters like thickness, drug content, weight variation, moisture absorption and drug permeation studies were evaluated for the prepared patches. No significant difference in thickness, average weight and in the drug content among the patches.Results:It was observed that from hydrophilic polymers the drug release was found to be faster compared to (F5 and F6 & F3 and F4) combination of hydrophilic and lipophilic polymers used in the study. Patches containing HPMC and Sodium CMC (F5 and F6) showed faster release as the patches showed maximum percentage amount moisture absorption. The in vitro release data was treated with kinetic equations and it followed Higuchi's diffusion mechanism. The in vivo bioavailability study was performed in rats and observed that, drug reached to the peak in approximately 60 min (16%) after oral route of administration. However, approximately same amount of drug was found in the serum from transdermal formulation in 6 h and further increase in the amount of drug in the serum, indicated that the drug 5 bioavailability could be better and hence the hepatic metabolism can be avoided, as it is evident from the data. Further, the decrease in the amount of drug present in the serum 45 min after oral administration also indicated that major amount of drug might have got metabolized and the bioavailability is reduced. However, the transdermal patch released further amount of drug (33%) at the end of 24 h.Conclusion:The present study can be concluded that transdermal patch can extend the release of drug for many hours with better bioavailability and also can avoid the first pass effect.

Мета роботи. Узагальнити дані літературних джерел щодо переваг та недоліків, класифікації, особливостей технології трансдермальних терапевтичних систем.Матеріали і методи. У роботі використано методи інформаційного пошуку, аналізу даних літератури щодо трансдермальних систем та перспектив їх використання у медичній практиці.Результати й обговорення. Трансдермальні терапевтичні системи доставки лікарських речовин успішно розвиваються як альтернатива системному введенню ЛР та являють собою препарати, які наносяться на поверхню тіла і призначені для доставки певної дози активного фармацевтичного інгредієнта через шар шкіри безпосередньо в кров’яне русло або ж сприяють загоєнню травмованої ділянки тіла. Усі трансдермальні системи класифікують за трьома поколіннями розвитку. Залежно від методу введення лікарських речовин в систему, вони поділяються на три категорії: системи матричного, резервуарного та мікрорезервуарного типів.Висновки. Переваги таких лікарських засобів та позитивні рішення впровадження розробок трансдермальних терапевтичних систем у промислове виробництво активізували науково-дослідницьку діяльність у даному напрямку.

Recently, flexible transparent conductive films have received widespread attention as important components in the field of organic electronics. Herein, we propose a method for directly constructing flexible transparent conductive films on curved surfaces using silver nanowires as the primary conductive material with the assistance of ethyl cellulose. The uniform transparent conductive film is produced by spray coating the silver nanowires on the curved surface with a curvature diameter of 5 cm. The average sheet resistance is approximately 18.9 Ω sq–1 with a transparency reaching 92.33%, and the standard deviation of the surface resistance is 1.1 Ω sq–1. The inclusion of ethyl cellulose prevents the aggregation of silver nanowires and allows their even distribution on the film surface, which is crucial for achieving a uniform and stable transparent conductive film. Through the analysis and comparison of different types of cellulose, such as methyl cellulose, ethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, cellulose acetate, and cyanoethyl cellulose, a conclusion has been derived that only cellulose soluble in organic solvents can maintain a homogeneous distribution on the surface of the film without aggregation. Furthermore, changing the magnitude and sign of the curvature did not affect the uniformity of the film. The significant industrial potential of our approach lies in the direct construction of a uniformly transparent silver nanowire network on curved surfaces with applications spanning various fields. Specifically, it can be employed in the realm of electronics, catering to the needs of touchscreens in electronic displays, solar cells, and flexible electronic devices, such as flexible circuit boards.

The main aim of this study was to expand the present formulation with patch and to evaluate the transdermal patches of Flurbiprofen, NSAID (Non-Steroidal Anti-Inflammatory Drug) used in the treatment of arthritis. Flurbiprofen is required at a sustained rate of its short half- life (3-4 hours) long term percutaneous absorption is required for its gastrointestinal side effects. Hence in this study, an effort was done to develop transdermal patches of Flurbiprofen by employing a different combination of polymers were prepared by the solvent evaporation technique. Nine formulations were prepared consists of Hydroxy Propyl Methyl Cellulose (HPMC) E15 and polyvinylpyrrolidone in the ratios of 1:1, 1:2. Formulation, HPMC E15 and Ethylcellulose (EC) in 1:1, 1:2. Formulations, HPMC E15 and Eudragit RS100 in 1:1, 1:2, and Formulation HPMC E15 and Eudragit RL100 in 1:1, 1:2.Formulations (F1- F8). F9 formulations contain HPMC E15, Eudragit RS100 in 2:1 ratio with permeation enhancer DMSO 20% v/w of propylene glycol was used as a plasticizer in all the formulations. The developed patches were considered for several physicochemical parameters. In vitro drug release studies showed maximum percentage in 24 hrs for F9 formulation 94.31±1.43, showed maximum Ex-vivo skin permeation of 10,120±0.91 µg/cm2, and the obtained flux meets the required flux. The resultant data was fitted into zero; first, Higuchi and Peppas model and Formulation F9 followed zero order. Drug compatibility studies were resulted by FTIR. The results specify that Flurbiprofen transdermal patch can be designed with the required amount of flux with desire mechanical properties for the cause of better therapeutic benefits.

Ordered, templated, thin films of ethyl(hydroxyethyl)cellulose (EHEC) were produced on a freshly cleaved crystalline graphite surface by exploiting the nature of sodium dodecyl sulfate adsorption (SDS) and its interaction with EHEC. The films were prepared by exposing the graphite surface to a dilute aqueous solution containing EHEC−SDS mixtures, followed by rinsing to remove the SDS and drying. The structure of the remaining EHEC film at the graphite−air interface was investigated by atomic force microscopy and compared with images of SDS and EHEC polymer on adsorbed graphite obtained in separate experiments. The results showed that polymer networks were formed from the EHEC−SDS mixture (after rinsing out the SDS), which were predominately aligned in one of three preferential directions separated by 60°, presumably as a result of templating by coadsorbed SDS. In addition, the alignment of the EHEC polymer and spacing between the polymer strands was found to be a function of surfactant concentration. Film...

Influence of the functionalization pattern of ethyl cellulose on the interactions with polystyrene latex particles in aqueous mixtures

A nonsteroidal drug called flurbiprofen (FBN) has analgesic, anti-inflammatory and antipyretic activity. Currently the determination of FBN in cataplasm does not have any pharmacopeial method. However, the drug substance, tablet and ophthalmic solution formulations do have pharmacopeial methods. The development and validation of an accurate, precise and stability-indicating analytical method for the determination of FBN in cataplasm formulations is reported. The gradient method was employed for the quantification of FBN in the presence of internal standards such as biphenyl. A nonpolar separation phase (C18 , 250 × 4.6 mm, 5 μm Inertsil column; GL Sciences) was used. The optimal flow rate, column oven temperature, injection volume and detector wavelengths were 1.0 ml/min, 40°C, 20 μl and 245 nm, respectively. Mobile phase A was a mixture of water and glacial acetic acid (30:1 v/v) pH adjusted to 2.20 with glacial acetic acid or 1m NaOH; mobile phase B was methanol (100%). The gradient elution program was [time (min)/% B]: 5/60, 20/70, 25/70, 30/60 and 40/60. The obtained RSDs for the precision and intermediate precision were 0.7 and 0.5%. The percentage recovery ranged from 99.2 to 100.4%. The linear regression coefficient >0.9996 indicates that all peak responses were linear with the concentration. The sample and standard solutions were stable for up to 24 h on the benchtop and in the refrigerator. The critical peaks were well separated from the generated peaks owing to forced degradation, including diluent and placebo peaks. The method validation data and quality by design-based robustness study results indicate that the developed method is robust and fit for routine use in the quality control laboratory. The proposed method is specific, accurate and precise, and the quality by design utilized the first method for the determination of FBN in cataplasm formulations. Transdermal patches and gels have low extraction capacity and this method is applicable for quantification.

In past years, various studies have considered transdermal drug delivery system for improving patient compliance. One approach to deliver drug via transdermal route is transdermal patch. These patches include single-layer drug in adhesive patches and micro reservoir transdermal patch & matrix system. Acrylic-acid, hydroxypropyl methylcellulose (HPMC) and polyethylene glycol are commonly used polymers for manufacturing of transdermal patches. Characterization of patches includes patch thickness, weight uniformity, irritation studies, in-vitro drug release and permeation studies. This review summarizes various polymers, types of transdermal patches and evaluation of transdermal patches based on up-to-date data extracted from reputed journals and official websites.

The objective of the present study was to formulate and evaluate a press coated pulsatile drug delivery system of salbutamol sulphate in order to attain a time controlled release for treatment of nocturnal asthma. The core was prepared by direct compression, while press coating technique was used in coating the outer layer there by preparing a press coated tablet. The immediate release core formulations comprised of salbutamol sulphate and disintegrants like crospovidone, croscarmellose sodium and sodium starch glycolate in different ratios with the drug. The outer coat formulations were prepared using a hydrophilic (HPMC) and hydrophobic (EC) polymer of similar viscosity. The polymers were reviewed individually for their influence on lag time further obtaining the lag time using polymer combinations were assessed by employing central composite design. All the preliminary trials were evaluated for various post compression parameters along with the dissolution study that was performed using USP paddle method at 50 rpm in 0.1 N HCl and phosphate buffer pH 6.8. The formulation containing 300 mg of EC N50 and 75‑100 mg of HPMC E50 may be regarded as the minimum quantity required in outer press coat so as to attain a predetermined lag time of 6 h. Key words: Central composite design, ethylcellulose, hydroxypropyl methylcellulose, press coat, salbutamol sulphate, time controlled release

The aim of the present work was to develop controlled release matrix formulation of nifedipine and investigate the effects of both hydrophilic and hydrophobic polymers on in vitro drug release. Matrix tablets were prepared by wet granulation technique using different concentration of hydroxy propyl methyl cellulose (HPMC), ethyl cellulose (EC), compressible Eudragits (RSpo and RLpo) and their combination in different ratios to examine their influence on tablet properties and drug release profile.Tablets were evaluated by measurement of hardness, friability, content uniformity, weight variation and drug release pattern. Release studies were carried out using USP type II apparatus in 900 ml of sodium phosphate buffer (pH 7.4) with 0.5% (w/v) SDS. The amount of drug released was determined at 238 nm by UV-visible spectrophotometer. In vitro dissolution studies indicated that hydrophobic polymers significantly reduced the rate of drug release compared to hydrophilic ones in 12 hrs and combination of both polymers exhibited the best release profile to sustain the drug release for prolong period of time. As a result, the tablet containing HPMC:EC in ratio of 0.75:1 showed better controlled release pattern over a period of 12 hrs. In selected formulation, the calculated regression coefficients for release models fitted best to zero-order models

Micro-mechanical properties of drying material bridges of pharmaceutical excipients

The oral mucosa is vascularized where by absorbed drugs get direct access to the systemic circulation without first pass metabolism. This present work is to formulate mouth dissolving film of Ezetamibe for enhanced bioavalibility. Drug and excipients studies were conducted using FTIR. Oral films of Ezetamibe were formulated using HPMC E5, as a film forming agent and propylene glycol as plasticize. And citricacid (salaviry stimulent), flavouring agents (vennila) are used.The solvent casting method was used for the preparation of films. Ezetamibe oral film was evaluated for folding endurance, thickness, weight variation test, surface pH, content uniformity,dissolving time and in-vitro dissolution. No drug–excipients interaction was observed. The characterization studies depict the purity of drug and all the excipients used in the formulation. The IR spectrum of mixture of Ezetamibe with all other excipients does not show any changes which indicate its compatibility with other excipients. From the results, it can be concluded that the fast dissolving oral film of Ezetamibe showed fast disintegration, dissolution of drug in salivary pH. Thus the prepared fast dissolving films of Ezetamibe could be a better alternative for achieving rapid oral bio availability. Keywords: Ezetamibe, hypercholesterolaemia,HPMC,